long-term effects of an intensive lifestyle intervention...

Long-Term Effects of an Intensive Lifestyle Intervention on Electrocardiographic Evidence of Left Ventricular Hypertrophy: The Action for Health in Diabetes (Look AHEAD) Trial

Tina Brinkley, PhDDepartment of Internal MedicineWake Forest School of Medicine

Tina Brinkley, PhDLong-Term Effects of an Intensive Lifestyle Intervention on

Electrocardiographic Evidence of Left Ventricular Hypertrophy: The Action for Health in Diabetes (Look

AHEAD) Trial

FINANCIAL DISCLOSURE:

No relevant financial relationship exists

Presenter Disclosure Information Elements

Wake Forest Baptist Medical Center

Introduction – LV Hypertrophy (LVH)

• A marker of subclinical cardiac damage

• Characterized by enlargement and thickening of the LV

• Measured by echocardiography, MRI, ECG

• Differences in sensitivity, availability, cost

• ECG-LVH is an important clinical tool

• Strong predictor of future cardiovascular events

• Regression is associated with reduced risk

• Useful for assessing changes in CV risk over time


Introduction – LVH and Lifestyle

• LVH is prevalent in obesity and type 2 diabetes

• Exercise and weight loss are recommended to lower cardiovascular disease risk

• Some evidence of a benefit from therapeutic lifestyle changes

• Pharmacological intervention

• Diet/exercise interventions

• There are no RCT on long-term effects of weight loss on ECG-LVH


Purpose

To determine whether an intensive lifestyle intervention targeting weight loss reduces the incidence of ECG-LVH in overweight and obese adults with type 2 diabetes


Methods: Look AHEAD

• Multi-center randomized clinical trial

• 5,145 study participants

• 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE)

• ILI: 7% weight loss; 1200-1800 kcal/day; 175 min/week of physical activity

• DSE: education, social support


Methods: Study Population

• Age: 45 to 76 years

• Overweight or obese (BMI ≥25 kg/m2 or ≥27 kg/m2 if taking insulin

• Type 2 diabetes

• Excluded prevalent ECG-LVH (5%)


Methods: Electrocardiography

• Resting ECGs were performed every 2 years

• Outcomes of Interest

1) ECG-LVH (Cornell voltage)

• RaVL + SV3 >2800 μV in men and >2000 μV in women

2) Continuous Cornell voltage


Statistical Analyses (n=4,548)

• Proportional hazards regression was used to compare the incidence of ECG-LVH (defined as time to first occurrence)

• Mixed models were used to compare changes in absolute Cornell voltage over time

• Tests of interactions by sex, race/ethnicity and baseline CVD status

• Analyses were performed according to the intention-to-treat principle

• All available follow-up data were included


Results: Baseline DemographicsOverallN=4,548

DSEN=2,261

ILIN=2,287 p value

Age (years) 58.7±6.8 58.9±6.9 58.5±6.8 0.08

Gender WomenMen

2641 (58.1)1907 (41.9)

1318 (58.3)943 (41.7)

1323 (57.9)964 (42.1)

0.76

Race/ethnicityAfrican AmericanNative American HispanicNon-Hispanic WhiteOther/Mixed

676 (14.9)230 (5.1)

575 (12.7)2933 (64.5)133 (2.9)

340 (15.0)114 (5.0)

284 (12.6)1459 (64.5)

64 (2.8)

336 (14.7)116 (5.1)

291 (12.7)1474 (64.5)

69 (3.0)

0.99

History of CVDYesNo

615 (13.5)3933 (86.5)

293 (13.0)1968 (87.0)

322 (14.1)1965 (85.9)

0.27

Use of antihypertensive agentsYesNo

3214 (71.7)1268 (28.3)

1580 (71.2)638 (28.8)

1634 (72.2)630 (27.8)

0.49

Blood pressure (mmHg)SystolicDiastolic

128.3±17.070.0±9.5

129.0±16.970.2±9.6

127.6±17.169.8±9.5

0.0060.19


Results: Main Intervention Effects

The Look AHEAD Research Group. N Engl J Med 2013;369:145-154

↓3.5%

↓6.0%

↓1.1%

↑5.1%


Results: Overall Incident ECG-LVH

Incidence rates: 7.1% vs. 8.0%

HR = 0.88 (0.71-1.08) p=0.22

Cum

ulat

ive

Haz

ard

Years after randomization

____ DSE - - - ILI

Interactions:Sex: p=0.74Prior CVD: p=0.53Race: p=0.046


Results: ECG-LVH in WhitesC

umul

ativ

e H

azar

d


____ DSE - - - ILI

Incidence rate: 6.0%

HR = 1.07 (0.80-1.44); p=0.22


Results: ECG-LVH in HispanicsC

umul

ativ

e H

azar

d


____ DSE - - - ILI


HR = 1.05 (0.55-2.02); p=0.88


Results: ECG-LVH in Native AmericansC

umul

ativ

e H

azar

d


____ DSE - - - ILI


HR = 0.56 (0.29-1.09); p=0.09


Results: ECG-LVH in African AmericansC

umul

ativ

e H

azar

d


____ DSE - - - ILI


HR = 0.59 (0.39-0.92); p=0.02


Results: Sensitivity Analysis

Race / Ethnicity

Hazard Ratios for ILI vs DSE adjusted for

treatment arm, race, armx race*

Hazard Ratios for ILI vs DSE further adjusted for change in SBP and BP

drug use**

HR 95% CI HR 95% CI

White 1.07 0.79 1.44 1.03 0.76 1.40

African American 0.57 0.37 0.88 0.59 0.38 0.92

Hispanic 1.12 0.58 2.16 1.12 0.58 2.16

Native American 0.56 0.29 1.09 0.53 0.26 1.07

Other/Mixed 4.10 0.48 35.7 4.37 0.51 37.0

*Interaction p-value = 0.046**Interaction p-value = 0.065


Results: Cornell Voltage (CV)

Intervention by year interaction: p = 0.63Average intervention difference over time:12.48 μV (95%CI: -1.79 to 26.74), p = 0.09

Cha

nge

in A

djus

ted

Mea

n C

V (μ

V)


____ DSE - - - ILI

Interactions:Sex: p=0.70Prior CVD: p=0.56Race: p=0.70


Summary

• A long-term intensive lifestyle intervention in overweight and obese adults with type 2 diabetes does not significantly lower overall incident ECG-LVH

• The protective effect of the lifestyle intervention observed in African Americans, however, warrants further investigation


Strengths and Limitations

Limitations

• Limited generalizability (T2DM, volunteer)

• Indirect measure of LVH

• Several different criteria for ECG-LVH

Strengths

• Large, well-characterized cohort

• Good retention

• Many years of follow-up


Future Analyses

• Identify possible mechanisms for race-specific findings

• Explore other relevant factors

• Fitness vs. Fatness

• Glycemic control, statin use

• Examine regression of ECG-LVH (5.1% prevalence at baseline)


AcknowledgementsCoauthors Funding Support for Look AHEAD

Wake Forest University Mark A. Espeland, PhDElsayed Z. Soliman, MDAlain G. Bertoni, MD, MPHAndrea Anderson, MS

Pennington Biomedical Research CenterFrank L. Greenway, MD

NIDDKWilliam C. Knowler, MD, DrPH

University of Alabama at BirminghamStephen P. Glasser, MD

Joslin Diabetes Center, HarvardEdward S. Horton, MD

Look AHEAD was supported by DHHS/NIHcooperative agreements (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992); National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women’s Health; and the Centers for Disease Control and Prevention; the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) provided personnel, medical oversight, and use of facilities.


THANK YOU

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